SummaryThere is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the “graphene family” are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials “beyond graphene” (BEG) will have to meet – like graphene – the following criteria:
(1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range),
(2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and
(3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties.
In contrast to the existing “graphene family”,
(4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs).
Moreover – and unlike – many covalent organic frameworks (COFs),
(5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale.
The potential to make 2D materials “beyond graphene” is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the “graphene family” with triazine-based graphitic carbon, a compound highlighted as an “emerging competitor for the miracle material” graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.

There is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the “graphene family” are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials “beyond graphene” (BEG) will have to meet – like graphene – the following criteria:
(1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range),
(2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and
(3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties.
In contrast to the existing “graphene family”,
(4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs).
Moreover – and unlike – many covalent organic frameworks (COFs),
(5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale.
The potential to make 2D materials “beyond graphene” is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the “graphene family” with triazine-based graphitic carbon, a compound highlighted as an “emerging competitor for the miracle material” graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.

SummaryThe aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction.
In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases.
BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.

The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction.
In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases.
BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.

Max ERC Funding

1 920 697 €

Duration

Start date: 2017-06-01, End date: 2022-05-31

Project acronymBetaDropNMR

ProjectUltra-sensitive NMR in liquids

Researcher (PI)Magdalena Kowalska-Wyrowska

Host Institution (HI)EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH

Call DetailsStarting Grant (StG), PE2, ERC-2014-STG

Summary"The nuclear magnetic resonance spectroscopy (NMR) is a versatile and powerful tool, especially in chemistry and in biology. However, its limited sensitivity and small amount of suitable probe nuclei pose severe constraints on the systems that may be explored.
This project aims at overcoming the above limitations by giving NMR an ultra-high sensitivity and by enlarging the NMR ""toolbox"" to dozens of nuclei across the periodic table. This will be achieved by applying the β-NMR method to the soft matter samples. The method relies on anisotropic emission of β particles in the decay of highly spin-polarized nuclei. This feature results in 10 orders of magnitude more sensitivity compared to conventional NMR and makes it applicable to elements which are otherwise difficult to investigate spectroscopically. β-NMR has been successfully applied in nuclear physics and material science in solid samples and high-vacuum environments, but never before to liquid samples placed in atmospheric pressure. With this novel approach I want to create a new universal and extremely sensitive tool to study various problems in biochemistry.
The first questions which I envisage addressing with this ground-breaking and versatile method concern the interaction of essential metal ions, which are spectroscopically silent in most techniques, Mg2+, Cu+, and Zn2+, with proteins and nucleic acids. The importance of these studies is well motivated by the fact that half of the proteins in our human body contain metal ions, but their interaction mechanism and factors influencing it are still not fully understood. In this respect NMR spectroscopy is of great help: it provides information on the structure, dynamics, and chemical properties of the metal complexes, by revealing the coordination number, oxidation state, bonding situation and electronic configuration of the interacting metal.
My long-term aim is to establish a firm basis for β-NMR in soft matter studies in biology, chemistry and physics."

"The nuclear magnetic resonance spectroscopy (NMR) is a versatile and powerful tool, especially in chemistry and in biology. However, its limited sensitivity and small amount of suitable probe nuclei pose severe constraints on the systems that may be explored.
This project aims at overcoming the above limitations by giving NMR an ultra-high sensitivity and by enlarging the NMR ""toolbox"" to dozens of nuclei across the periodic table. This will be achieved by applying the β-NMR method to the soft matter samples. The method relies on anisotropic emission of β particles in the decay of highly spin-polarized nuclei. This feature results in 10 orders of magnitude more sensitivity compared to conventional NMR and makes it applicable to elements which are otherwise difficult to investigate spectroscopically. β-NMR has been successfully applied in nuclear physics and material science in solid samples and high-vacuum environments, but never before to liquid samples placed in atmospheric pressure. With this novel approach I want to create a new universal and extremely sensitive tool to study various problems in biochemistry.
The first questions which I envisage addressing with this ground-breaking and versatile method concern the interaction of essential metal ions, which are spectroscopically silent in most techniques, Mg2+, Cu+, and Zn2+, with proteins and nucleic acids. The importance of these studies is well motivated by the fact that half of the proteins in our human body contain metal ions, but their interaction mechanism and factors influencing it are still not fully understood. In this respect NMR spectroscopy is of great help: it provides information on the structure, dynamics, and chemical properties of the metal complexes, by revealing the coordination number, oxidation state, bonding situation and electronic configuration of the interacting metal.
My long-term aim is to establish a firm basis for β-NMR in soft matter studies in biology, chemistry and physics."

Max ERC Funding

1 500 000 €

Duration

Start date: 2015-10-01, End date: 2020-09-30

Project acronymBIDECASEOX

ProjectBio-inspired Design of Catalysts for Selective Oxidations of C-H and C=C Bonds

Researcher (PI)Miguel Costas Salgueiro

Host Institution (HI)UNIVERSITAT DE GIRONA

Call DetailsStarting Grant (StG), PE5, ERC-2009-StG

SummaryThe selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.

The selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.

Max ERC Funding

1 299 998 €

Duration

Start date: 2009-11-01, End date: 2015-10-31

Project acronymBinGraSp

ProjectModeling the Gravitational Spectrum of Neutron Star Binaries

Researcher (PI)Sebastiano Bernuzzi

Host Institution (HI)FRIEDRICH-SCHILLER-UNIVERSITAT JENA

Call DetailsStarting Grant (StG), PE2, ERC-2016-STG

SummaryThe most energetic electromagnetic phenomena in the Universe are believed to be powered by the collision of two neutron stars, the smallest and densest stars on which surface gravity is about 2 billion times stronger than gravity on Earth. However, a definitive identification of neutron star mergers as central engines for short-gamma-ray bursts and kilonovae transients is possible only by direct gravitational-wave observations. The latter provide us with unique information on neutron stars' masses, radii, and spins, including the possibility to set the strongest observational constraints on the unknown equation-of-state of matter at supranuclear densities.
Neutron stars binary mergers are among the main targets for ground-based gravitational-wave interferometers like Advanced LIGO and Virgo, which start operations this year. The astrophysical data analysis of the signals emitted by these sources requires the availability of accurate waveform models, which are missing to date. Hence, the theoretical understanding of the gravitational spectrum is a necessary and urgent step for the development of a gravitational-based astrophysics in the next years.
This project aims at developing, for the first time, a precise theoretical model for the complete gravitational spectrum of neutron star binaries, including the merger and postmerger stages of the coalescence process. Building on the PI's unique expertise and track record, the proposed research exploits synergy between analytical and numerical methods in General Relativity. Results from state of the art nonlinear 3D numerical relativity simulations will be combined with the most advanced analytical framework for the relativistic two-body problem. The model developed here will be used in the first gravitational-wave observations and will dramatically impact multimessenger astrophysics.

The most energetic electromagnetic phenomena in the Universe are believed to be powered by the collision of two neutron stars, the smallest and densest stars on which surface gravity is about 2 billion times stronger than gravity on Earth. However, a definitive identification of neutron star mergers as central engines for short-gamma-ray bursts and kilonovae transients is possible only by direct gravitational-wave observations. The latter provide us with unique information on neutron stars' masses, radii, and spins, including the possibility to set the strongest observational constraints on the unknown equation-of-state of matter at supranuclear densities.
Neutron stars binary mergers are among the main targets for ground-based gravitational-wave interferometers like Advanced LIGO and Virgo, which start operations this year. The astrophysical data analysis of the signals emitted by these sources requires the availability of accurate waveform models, which are missing to date. Hence, the theoretical understanding of the gravitational spectrum is a necessary and urgent step for the development of a gravitational-based astrophysics in the next years.
This project aims at developing, for the first time, a precise theoretical model for the complete gravitational spectrum of neutron star binaries, including the merger and postmerger stages of the coalescence process. Building on the PI's unique expertise and track record, the proposed research exploits synergy between analytical and numerical methods in General Relativity. Results from state of the art nonlinear 3D numerical relativity simulations will be combined with the most advanced analytical framework for the relativistic two-body problem. The model developed here will be used in the first gravitational-wave observations and will dramatically impact multimessenger astrophysics.

Max ERC Funding

1 432 301 €

Duration

Start date: 2017-10-01, End date: 2022-09-30

Project acronymBIO-H-BORROW

ProjectBiocatalytic Amine Synthesis via Hydrogen Borrowing

Researcher (PI)Nicholas TURNER

Host Institution (HI)THE UNIVERSITY OF MANCHESTER

Call DetailsAdvanced Grant (AdG), PE5, ERC-2016-ADG

SummaryAmine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen.
In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source.
The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.

Amine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen.
In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source.
The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.

Max ERC Funding

2 337 548 €

Duration

Start date: 2017-06-01, End date: 2022-05-31

Project acronymBIOINCMED

ProjectBioinorganic Chemistry for the Design of New Medicines

Researcher (PI)Peter John Sadler

Host Institution (HI)THE UNIVERSITY OF WARWICK

Call DetailsAdvanced Grant (AdG), PE5, ERC-2009-AdG

SummaryBioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.

Bioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.

Max ERC Funding

1 565 397 €

Duration

Start date: 2010-07-01, End date: 2015-12-31

Project acronymBIOINOHYB

ProjectSmart Bioinorganic Hybrids for Nanomedicine

Researcher (PI)Cristiana Di Valentin

Host Institution (HI)UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA

Call DetailsConsolidator Grant (CoG), PE5, ERC-2014-CoG

SummaryThe use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.

The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.

SummaryFrom a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities.
I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences.
This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.

From a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities.
I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences.
This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.

Max ERC Funding

2 497 044 €

Duration

Start date: 2011-05-01, End date: 2016-04-30

Project acronymBioMet

ProjectSelective Functionalization of Saturated Hydrocarbons

Researcher (PI)Ilan MAREK

Host Institution (HI)TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY

Call DetailsAdvanced Grant (AdG), PE5, ERC-2017-ADG

SummaryDespite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.

Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.

Max ERC Funding

2 499 375 €

Duration

Start date: 2018-11-01, End date: 2023-10-31

Project acronymBIOMIM

ProjectBiomimetic films and membranes as advanced materials for studies on cellular processes

Researcher (PI)Catherine Cecile Picart

Host Institution (HI)INSTITUT POLYTECHNIQUE DE GRENOBLE

Call DetailsStarting Grant (StG), PE5, ERC-2010-StG_20091028

SummaryThe main objective nowadays in the field of biomaterials is to design highly performing bioinspired materials learning from natural processes. Importantly, biochemical and physical cues are key parameters that can affect cellular processes. Controlling processes that occur at the cell/material interface is also of prime importance to guide the cell response. The main aim of the current project is to develop novel functional bio-nanomaterials for in vitro biological studies. Our strategy is based on two related projects.
The first project deals with the rational design of smart films with foreseen applications in musculoskeletal tissue engineering. We will gain knowledge of key cellular processes by designing well defined self-assembled thin coatings. These multi-functional surfaces with bioactivity (incorporation of growth factors), mechanical (film stiffness) and topographical properties (spatial control of the film s properties) will serve as tools to mimic the complexity of the natural materials in vivo and to present bioactive molecules in the solid phase. We will get a better fundamental understanding of how cellular functions, including adhesion and differentiation of muscle cells are affected by the materials s surface properties.
In the second project, we will investigate at the molecular level a crucial aspect of cell adhesion and motility, which is the intracellular linkage between the plasma membrane and the cell cytoskeleton. We aim to elucidate the role of ERM proteins, especially ezrin and moesin, in the direct linkage between the plasma membrane and actin filaments. Here again, we will use a well defined microenvironment in vitro to simplify the complexity of the interactions that occur in cellulo. To this end, lipid membranes containing a key regulator lipid from the phosphoinositides familly, PIP2, will be employed in conjunction with purified proteins to investigate actin regulation by ERM proteins in the presence of PIP2-membranes.

The main objective nowadays in the field of biomaterials is to design highly performing bioinspired materials learning from natural processes. Importantly, biochemical and physical cues are key parameters that can affect cellular processes. Controlling processes that occur at the cell/material interface is also of prime importance to guide the cell response. The main aim of the current project is to develop novel functional bio-nanomaterials for in vitro biological studies. Our strategy is based on two related projects.
The first project deals with the rational design of smart films with foreseen applications in musculoskeletal tissue engineering. We will gain knowledge of key cellular processes by designing well defined self-assembled thin coatings. These multi-functional surfaces with bioactivity (incorporation of growth factors), mechanical (film stiffness) and topographical properties (spatial control of the film s properties) will serve as tools to mimic the complexity of the natural materials in vivo and to present bioactive molecules in the solid phase. We will get a better fundamental understanding of how cellular functions, including adhesion and differentiation of muscle cells are affected by the materials s surface properties.
In the second project, we will investigate at the molecular level a crucial aspect of cell adhesion and motility, which is the intracellular linkage between the plasma membrane and the cell cytoskeleton. We aim to elucidate the role of ERM proteins, especially ezrin and moesin, in the direct linkage between the plasma membrane and actin filaments. Here again, we will use a well defined microenvironment in vitro to simplify the complexity of the interactions that occur in cellulo. To this end, lipid membranes containing a key regulator lipid from the phosphoinositides familly, PIP2, will be employed in conjunction with purified proteins to investigate actin regulation by ERM proteins in the presence of PIP2-membranes.

SummaryThis ERC-StG proposal, BIOMOF, outlines a dual strategy for the growth and processing of porous metal-organic framework (MOF) materials, inspired by the interfacial interactions that characterise highly controlled biomineralisation processes. The aim is to prepare MOF (bio)-composite materials of hierarchical structure and multi-modal functionality to address key societal challenges in healthcare, catalysis and energy. In order for MOFs to reach their full potential, a transformative approach to their growth, and in particular their processability, is required since the insoluble macroscopic micron-sized crystals resulting from conventional syntheses are unsuitable for many applications. The BIOMOF project defines chemically flexible routes to MOFs under mild conditions, where the added value with respect to wide-ranging experimental procedures for the growth and processing of crystalline controllably nanoscale MOF materials with tunable structure and functionality that display significant porosity for wide-ranging applications is extremely high. Theme 1 exploits protein vesicles and abundant biopolymer matrices for the confined growth of soluble nanoscale MOFs for high-end biomedical applications such as cell imaging and targeted drug delivery, whereas theme 2 focuses on the cost-effective preparation of hierarchically porous MOF composites over several length scales, of relevance to bulk industrial applications such as sustainable catalysis, separations and gas-storage. This diverse yet complementary range of applications arising simply from the way the MOF is processed, coupled with the versatile structural and physical properties of MOFs themselves indicates strongly that the BIOMOF concept is a powerful convergent new approach to applied materials chemistry.

This ERC-StG proposal, BIOMOF, outlines a dual strategy for the growth and processing of porous metal-organic framework (MOF) materials, inspired by the interfacial interactions that characterise highly controlled biomineralisation processes. The aim is to prepare MOF (bio)-composite materials of hierarchical structure and multi-modal functionality to address key societal challenges in healthcare, catalysis and energy. In order for MOFs to reach their full potential, a transformative approach to their growth, and in particular their processability, is required since the insoluble macroscopic micron-sized crystals resulting from conventional syntheses are unsuitable for many applications. The BIOMOF project defines chemically flexible routes to MOFs under mild conditions, where the added value with respect to wide-ranging experimental procedures for the growth and processing of crystalline controllably nanoscale MOF materials with tunable structure and functionality that display significant porosity for wide-ranging applications is extremely high. Theme 1 exploits protein vesicles and abundant biopolymer matrices for the confined growth of soluble nanoscale MOFs for high-end biomedical applications such as cell imaging and targeted drug delivery, whereas theme 2 focuses on the cost-effective preparation of hierarchically porous MOF composites over several length scales, of relevance to bulk industrial applications such as sustainable catalysis, separations and gas-storage. This diverse yet complementary range of applications arising simply from the way the MOF is processed, coupled with the versatile structural and physical properties of MOFs themselves indicates strongly that the BIOMOF concept is a powerful convergent new approach to applied materials chemistry.

Max ERC Funding

1 492 970 €

Duration

Start date: 2010-11-01, End date: 2015-10-31

Project acronymBIONICS

ProjectBio-Inspired Routes for Controlling the Structure and Properties of Materials: Reusing proven tricks on new materials

Researcher (PI)Boaz Pokroy

Host Institution (HI)TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY

Call DetailsStarting Grant (StG), PE5, ERC-2013-StG

Summary"In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select.
I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials.
The three bio-inspired strategies that we will utilize are:
(i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase;
(ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature;
(iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure.
The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us
(1) to produce single, intricately shaped crystals without the need to etch, drill or polish;
(2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase;
(3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."

"In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select.
I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials.
The three bio-inspired strategies that we will utilize are:
(i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase;
(ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature;
(iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure.
The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us
(1) to produce single, intricately shaped crystals without the need to etch, drill or polish;
(2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase;
(3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."

Max ERC Funding

1 500 000 €

Duration

Start date: 2013-09-01, End date: 2018-08-31

Project acronymBlackHoleMaps

ProjectMapping gravitational waves from collisions of black holes

Researcher (PI)Mark Douglas Hannam

Host Institution (HI)CARDIFF UNIVERSITY

Call DetailsConsolidator Grant (CoG), PE2, ERC-2014-CoG

SummaryBreakthroughs in numerical relativity in 2005 gave us unprecedented access to the strong-field regime of general relativity, making possible solutions of the full nonlinear Einstein equations for the merger of two black holes. Numerical relativity is also crucial to study fundamental physics with gravitational-wave (GW) observations: numerical solutions allow us to construct models that will be essential to extract physical information from observations in data from Advanced LIGO and Virgo, which will operate from late 2015. Complete signal models will allow us to follow up our first theoretical predictions of the nature of black-hole mergers with their first observational measurements.
The goal of this project is to advance numerical-relativity methods, deepen our understanding of black-hole mergers, and map the parameter space of binary configurations with the most comprehensive and systematic set of numerical calculations performed to date, in order to produce a complete GW signal model. Central to this problem is the purely general-relativistic effect of orbital precession. The inclusion of precession in waveform models is the most challenging and urgent theoretical problem in the build-up to GW astronomy. Simulations must cover a seven-dimensional parameter space of binary configurations, but their computational cost makes a naive covering unfeasible. This project capitalizes on a breakthrough preliminary model produced by my team in 2013, with the pragmatic goal of focussing on the physics that will be measurable with GW detectors over the next five years.
My team at Cardiff is uniquely placed to tackle this problem. Since 2005 I have been at the forefront of black-hole simulations and waveform modelling, and the Cardiff group is a world leader in analysis of GW detector data. This project will consolidate my team to make breakthroughs in strong-field gravity, astrophysics, fundamental physics and cosmology using GW observations.

Breakthroughs in numerical relativity in 2005 gave us unprecedented access to the strong-field regime of general relativity, making possible solutions of the full nonlinear Einstein equations for the merger of two black holes. Numerical relativity is also crucial to study fundamental physics with gravitational-wave (GW) observations: numerical solutions allow us to construct models that will be essential to extract physical information from observations in data from Advanced LIGO and Virgo, which will operate from late 2015. Complete signal models will allow us to follow up our first theoretical predictions of the nature of black-hole mergers with their first observational measurements.
The goal of this project is to advance numerical-relativity methods, deepen our understanding of black-hole mergers, and map the parameter space of binary configurations with the most comprehensive and systematic set of numerical calculations performed to date, in order to produce a complete GW signal model. Central to this problem is the purely general-relativistic effect of orbital precession. The inclusion of precession in waveform models is the most challenging and urgent theoretical problem in the build-up to GW astronomy. Simulations must cover a seven-dimensional parameter space of binary configurations, but their computational cost makes a naive covering unfeasible. This project capitalizes on a breakthrough preliminary model produced by my team in 2013, with the pragmatic goal of focussing on the physics that will be measurable with GW detectors over the next five years.
My team at Cardiff is uniquely placed to tackle this problem. Since 2005 I have been at the forefront of black-hole simulations and waveform modelling, and the Cardiff group is a world leader in analysis of GW detector data. This project will consolidate my team to make breakthroughs in strong-field gravity, astrophysics, fundamental physics and cosmology using GW observations.

SummaryBorylated molecules and polymers are of great interest due to their broad application in organic synthesis and materials science. The functionalisation of organic substrates with boryl groups R2B is based on classical synthetic methods e.g. hydro- and diboration of C-C multiple bonds. Likewise, borylenes B-R should be versatile reagents for corresponding functionalisations, however, the chemistry of such species remained unexplored due to their high instability.
Pioneering work in our laboratories has proven that complexes of the type [LxM=B-R] not only stabilise elusive borylenes B-R in the coordination sphere of various transition metals but, more importantly, serve as unprecedented sources for these species under ambient conditions in condensed phase. Thus, the major objective of the current proposal is to establish novel reactivity patterns based on B-R fragments for the functionalisation of organometallic and organic substrates. Particular attention will be paid to the synthesis of novel molecular and polymeric species with significant potential as materials. Given the pronounced importance of boron containing species in organic synthesis, catalysis and materials science, the proposed project is expected to have a significant impact on these areas of applied molecular science. In addition, a wide range of fundamental aspects will be covered, targeting e.g. novel conjugated cyclic systems or molecules with unprecedented boron-element combinations.
The following subjects will be pursued:
1)Cationic and anionic dimetalloborylenes as complementary building blocks in synthesis
2)Application of borylene metathesis in stoichiometric and catalytic transformations
3)Borylene transfer for organometallic synthesis and borylene based pi-conjugated materials

Borylated molecules and polymers are of great interest due to their broad application in organic synthesis and materials science. The functionalisation of organic substrates with boryl groups R2B is based on classical synthetic methods e.g. hydro- and diboration of C-C multiple bonds. Likewise, borylenes B-R should be versatile reagents for corresponding functionalisations, however, the chemistry of such species remained unexplored due to their high instability.
Pioneering work in our laboratories has proven that complexes of the type [LxM=B-R] not only stabilise elusive borylenes B-R in the coordination sphere of various transition metals but, more importantly, serve as unprecedented sources for these species under ambient conditions in condensed phase. Thus, the major objective of the current proposal is to establish novel reactivity patterns based on B-R fragments for the functionalisation of organometallic and organic substrates. Particular attention will be paid to the synthesis of novel molecular and polymeric species with significant potential as materials. Given the pronounced importance of boron containing species in organic synthesis, catalysis and materials science, the proposed project is expected to have a significant impact on these areas of applied molecular science. In addition, a wide range of fundamental aspects will be covered, targeting e.g. novel conjugated cyclic systems or molecules with unprecedented boron-element combinations.
The following subjects will be pursued:
1)Cationic and anionic dimetalloborylenes as complementary building blocks in synthesis
2)Application of borylene metathesis in stoichiometric and catalytic transformations
3)Borylene transfer for organometallic synthesis and borylene based pi-conjugated materials

SummaryThe study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.

The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.

Max ERC Funding

1 500 000 €

Duration

Start date: 2010-10-01, End date: 2015-09-30

Project acronymBrainBIT

ProjectAll-optical brain-to-brain behaviour and information transfer

Researcher (PI)Francesco PAVONE

Host Institution (HI)UNIVERSITA DEGLI STUDI DI FIRENZE

Call DetailsAdvanced Grant (AdG), PE2, ERC-2015-AdG

SummaryExchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.

Exchange of information between different brains usually takes place through the interaction between bodies and the external environment. The ultimate goal of this project is to establish a novel paradigm of brain-to-brain communication based on direct full-optical recording and controlled stimulation of neuronal activity in different subjects. To pursue this challenging objective, we propose to develop optical technologies well beyond the state of the art for simultaneous neuronal “reading” and “writing” across large volumes and with high spatial and temporal resolution, targeted to the transfer of advantageous behaviour in physiological and pathological conditions.
We will perform whole-brain high-resolution imaging in zebrafish larvae to disentangle the activity patterns related to different tasks. We will then use these patterns as stimulation templates in other larvae to investigate spatio-temporal subject-invariant signatures of specific behavioural states. This ‘pump and probe’ strategy will allow gaining deep insights into the complex relationship between neuronal activity and subject behaviour.
To move towards clinics-oriented studies on brain stimulation therapies, we will complement whole-brain experiments in zebrafish with large area functional imaging and optostimulation in mammals. We will investigate all-optical brain-to-brain information transfer to boost an advantageous behaviour, i.e. motor recovery, in a mouse model of stroke. Mice showing more effective responses to rehabilitation will provide neuronal activity templates to be elicited in other animals, in order to increase rehabilitation efficiency.
We strongly believe that the implementation of new technologies for all-optical transfer of behaviour between different subjects will offer unprecedented views of neuronal activity in healthy and injured brain, paving the way to more effective brain stimulation therapies.

SummaryExisting fluorescent molecular probes, due to limited brightness, do not allow imaging individual biomolecules directly in living cells, whereas bright fluorescent nanoparticles are unable to respond to single molecular stimuli and their inorganic core is not biodegradable. The aim of BrightSens is to develop ultrabright fluorescent organic nanoparticles (FONs) capable to convert single molecular stimuli into collective turn-on response of >100 encapsulated dyes, and to apply them in amplified molecular sensing of specific targets at the cell surface (receptors) and in the cytosol (mRNA). The project is composed of three work packages. (1) Synthesis of FONs: Dye-doped polymer and micellar FONs will be obtained by self-assembly. Molecular design of dyes and the use of bulky hydrophobic counterions will enable precise control of dyes organization inside FONs, which will resolve the fundamental problems of self-quenching and cooperative on/off switching in dye ensembles. (2) Synthesis of nanoprobes: Using cooperative Forster Resonance Energy Transfer from FONs to originally designed acceptor-sensor unit, we propose synthesis of the first nanoprobes that (a) undergo complete turn-on or colour switch in response to single molecular targets and (b) harvest light energy into photochemical disruption of cell membrane barriers. (3) Cellular applications: The obtained nanoprobes will be applied in 2D and 3D cultures of cancer cells for background-free single-molecule detection of membrane receptors and intracellular mRNA, which are important markers of cancer and apoptosis. An original concept of amplified photochemical internalization is proposed to trigger by light entry of nanoprobes into the cytosol. This high-risk/high-gain multidisciplinary project will result in new organic nanomaterials with unique photophysical properties that will enable visualization of biomolecules at work in living cells with expected impact on cancer research.

Existing fluorescent molecular probes, due to limited brightness, do not allow imaging individual biomolecules directly in living cells, whereas bright fluorescent nanoparticles are unable to respond to single molecular stimuli and their inorganic core is not biodegradable. The aim of BrightSens is to develop ultrabright fluorescent organic nanoparticles (FONs) capable to convert single molecular stimuli into collective turn-on response of >100 encapsulated dyes, and to apply them in amplified molecular sensing of specific targets at the cell surface (receptors) and in the cytosol (mRNA). The project is composed of three work packages. (1) Synthesis of FONs: Dye-doped polymer and micellar FONs will be obtained by self-assembly. Molecular design of dyes and the use of bulky hydrophobic counterions will enable precise control of dyes organization inside FONs, which will resolve the fundamental problems of self-quenching and cooperative on/off switching in dye ensembles. (2) Synthesis of nanoprobes: Using cooperative Forster Resonance Energy Transfer from FONs to originally designed acceptor-sensor unit, we propose synthesis of the first nanoprobes that (a) undergo complete turn-on or colour switch in response to single molecular targets and (b) harvest light energy into photochemical disruption of cell membrane barriers. (3) Cellular applications: The obtained nanoprobes will be applied in 2D and 3D cultures of cancer cells for background-free single-molecule detection of membrane receptors and intracellular mRNA, which are important markers of cancer and apoptosis. An original concept of amplified photochemical internalization is proposed to trigger by light entry of nanoprobes into the cytosol. This high-risk/high-gain multidisciplinary project will result in new organic nanomaterials with unique photophysical properties that will enable visualization of biomolecules at work in living cells with expected impact on cancer research.

Max ERC Funding

1 999 750 €

Duration

Start date: 2015-06-01, End date: 2020-05-31

Project acronymBSMFLEET

ProjectChallenging the Standard Model using an extended Physics program in LHCb

Researcher (PI)Diego Martinez Santos

Host Institution (HI)UNIVERSIDAD DE SANTIAGO DE COMPOSTELA

Call DetailsStarting Grant (StG), PE2, ERC-2014-STG

SummaryWe know that the Standard Model (SM) of Particle Physics is not the ultimate theory of Nature. It misses a quantum description of gravity, it does not offer any explanation to the composition of Dark Matter, and the matter-antimatter unbalance of the Universe is predicted to be significantly smaller than what we actually see. Those are fundamental questions that still need an answer. Alternative models to SM exist, based on ideas such as SuperSymmetry or extra dimensions, and are currently being tested at the Large Hadron Collider (LHC) at CERN. But after the first run of the LHC the SM is yet unbeaten at accelerators, which imposes severe constraints in Physics beyond the SM (BSM). From this point, I see two further working directions: on one side, we must increase our precision in the previous measurements in order to access smaller BSM effects. On the other hand; we should attack the SM with a new fleet of observables sensitive to different BSM scenarios, and make sure that we are making full use of what the LHC offers to us. I propose to create a team at Universidade de Santiago de Compostela that will expand the use of LHCb beyond its original design, while also reinforcing the core LHCb analyses in which I played a leading role so far. LHCb has up to now collected world-leading samples of decays of b and c quarks. My proposal implies to use LHCb for collecting and analysing also world-leading samples of rare s quarks complementary to those of NA62. In the rare s decays the SM sources of Flavour Violation have a stronger suppression than anywhere else, and therefore those decays are excellent places to search for new Flavour Violating sources that otherwise would be hidden behind the SM contributions. It is very important to do this now, since we may not have a similar opportunity in years. In addition, the team will also exploit LHCb to search for μμ resonances predicted in models like NMSSM, and for which LHCb also offers a unique potential that must be used.

We know that the Standard Model (SM) of Particle Physics is not the ultimate theory of Nature. It misses a quantum description of gravity, it does not offer any explanation to the composition of Dark Matter, and the matter-antimatter unbalance of the Universe is predicted to be significantly smaller than what we actually see. Those are fundamental questions that still need an answer. Alternative models to SM exist, based on ideas such as SuperSymmetry or extra dimensions, and are currently being tested at the Large Hadron Collider (LHC) at CERN. But after the first run of the LHC the SM is yet unbeaten at accelerators, which imposes severe constraints in Physics beyond the SM (BSM). From this point, I see two further working directions: on one side, we must increase our precision in the previous measurements in order to access smaller BSM effects. On the other hand; we should attack the SM with a new fleet of observables sensitive to different BSM scenarios, and make sure that we are making full use of what the LHC offers to us. I propose to create a team at Universidade de Santiago de Compostela that will expand the use of LHCb beyond its original design, while also reinforcing the core LHCb analyses in which I played a leading role so far. LHCb has up to now collected world-leading samples of decays of b and c quarks. My proposal implies to use LHCb for collecting and analysing also world-leading samples of rare s quarks complementary to those of NA62. In the rare s decays the SM sources of Flavour Violation have a stronger suppression than anywhere else, and therefore those decays are excellent places to search for new Flavour Violating sources that otherwise would be hidden behind the SM contributions. It is very important to do this now, since we may not have a similar opportunity in years. In addition, the team will also exploit LHCb to search for μμ resonances predicted in models like NMSSM, and for which LHCb also offers a unique potential that must be used.

Max ERC Funding

1 499 855 €

Duration

Start date: 2015-04-01, End date: 2020-03-31

Project acronymBSMOXFORD

ProjectPhysics Beyond the Standard Model at the LHC and with Atom Interferometers

Researcher (PI)Savas Dimopoulos

Host Institution (HI)EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH

Call DetailsAdvanced Grant (AdG), PE2, ERC-2008-AdG

SummaryElementary particle physics is entering a spectacular new era in which experiments at the Large Hadron Collider (LHC) at CERN will soon start probing some of the deepest questions in physics, such as: Why is gravity so weak? Do elementary particles have substructure? What is the origin of mass? Are there new dimensions? Can we produce black holes in the lab? Could there be other universes with different physical laws? While the LHC pushes the energy frontier, the unprecedented precision of Atom Interferometry, has pointed me to a new tool for fundamental physics. These experiments based on the quantum interference of atoms can test General Relativity on the surface of the Earth, detect gravity waves, and test short-distance gravity, charge quantization, and quantum mechanics with unprecedented precision in the next decade. This ERC Advanced grant proposal is aimed at setting up a world-leading European center for development of a deeper theory of fundamental physics. The next 10 years is the optimal time for such studies to benefit from the wealth of new data that will emerge from the LHC, astrophysical observations and atom interferometry. This is a once-in-a-generation opportunity for making ground-breaking progress, and will open up many new research horizons.

Elementary particle physics is entering a spectacular new era in which experiments at the Large Hadron Collider (LHC) at CERN will soon start probing some of the deepest questions in physics, such as: Why is gravity so weak? Do elementary particles have substructure? What is the origin of mass? Are there new dimensions? Can we produce black holes in the lab? Could there be other universes with different physical laws? While the LHC pushes the energy frontier, the unprecedented precision of Atom Interferometry, has pointed me to a new tool for fundamental physics. These experiments based on the quantum interference of atoms can test General Relativity on the surface of the Earth, detect gravity waves, and test short-distance gravity, charge quantization, and quantum mechanics with unprecedented precision in the next decade. This ERC Advanced grant proposal is aimed at setting up a world-leading European center for development of a deeper theory of fundamental physics. The next 10 years is the optimal time for such studies to benefit from the wealth of new data that will emerge from the LHC, astrophysical observations and atom interferometry. This is a once-in-a-generation opportunity for making ground-breaking progress, and will open up many new research horizons.